Multiple sclerosis (MS) is a debilitating inflammatory disease of the central nervous system (CNS) that is characterized by local destruction of the insulating myelin surrounding neuronal axons (Compston and Coles (2002) Lancet 359:1221-1231). With more than 200 million MS patients worldwide, there is great need for effective treatments that prevent progression or induce repair. Anti-inflammatory therapies have met with some success in preventing relapses (Bates (2011) Neurol. 76:S14-25). Some naturally occurring IgM antibodies identified from human serum can promote both cell signaling and remyelination of CNS lesions in an MS model involving chronic infection of susceptible mice by Theiler's encephalomyelitis virus (Warrington et al. (2000) Proc. Natl. Acad. Sci. USA 97:6820-6825) and in the lysolecithin model of focal demyelination (Bieber et al. (2002) Glia 3:241-249). This result raised the possibility that molecules with binding specificity for oligodendrocytes or myelin components may promote therapeutic remyelination in MS.